1. Field of the Invention
The present invention relates to the treatment of cancer cells, such as human prostate cancer cells and human gastric cancer cells, and particularly to cytotoxic compounds for the treatment of cancer cells which are gold(III) complexes of the type [(diaminocyclohexane)AuCl2] Cl.
2. Description of the Related Art
Cis-diamminedichloroplatinum(II) is an example of a commonly used platinum(II)-based anti-cancer drug. Continued usage of cis-diamminedichloroplatinum(II), unfortunately, has been found to lead to resistance to the drug in patients, along with a wide variety of undesirable side effects typically associated with chemotherapy treatments. Thus, alternative treatments which have the same efficacy of platinum(II)-based anti-cancer treatments are of great interest.
Gold(III) compounds have greatly attracted researchers' attention in the last decade for their outstanding cytotoxic actions. One such metal ion typically adopts a four-coordinate, square-planar geometry, thus is therefore expected to mimic the structural and electronic properties of platinum(II). Recent studies have shown that several gold(III) complexes are highly cytotoxic against different types of tumor cells, including some which are active even against the cis-diamminedichloroplatinum(II)-resistant cell lines.
The relationship to platinum(II) compounds makes gold(III) complexes good candidates for development and testing as anti-cancer drugs, although the relatively high kinetic ability and the often high redox potentials have largely hindered such investigations. In the early 1990's, a few gold compounds were prepared and characterized for their antitumor activity with positive results. Recently, using various Au(III) complexes with novel functionality has elicited further interest due to their distinct physical and chemical properties, stability under physiological conditions, and outstanding cytotoxic effects.
As noted above, cis-diamminedichloroplatinum(H) is one of the most widely used anti-cancer drugs today. However, platinum compounds possessing the 1,2-diaminocyclohexane (DACH) carrier ligand offer advantages over cis-diamminedichloroplatinum(II) with regard to bioavailability, activity and decreased renal toxicity. Over the past several years, significant effort has been devoted to study the antitumor activity of platinum-DACH complexes, whereas gold-DACH complexes have, up until now, received relatively little attention, despite the fact that Au(III) has a fairly rich biological chemistry. For example, Au(III) is redox active, can be coordinated by amino acids and proteins, is able to deprotonate and bind to the amide N of peptides, and is capable of cross-linking histidine imidazole rings.
As in the case of the parent cis-diamminedichloroplatinum(II), the antitumor activity of platinum-DACH is accompanied by some toxicity. The emergence of resistance and low water solubility that can affect the pharmacokinetics are additional features that must be improved in the quest for a more effective analog. Thus, it would be desirable to develop an anti-cancer treatment with the efficacy of platinum-DACH drugs, but with the preferable biological properties of Au(III).
Thus, cytotoxic compounds for treating cancer solving the aforementioned problems are desired.